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Penicillin / Penicillium Chrysogenum
Penicillin is a β-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually Gram-positive, organisms. The name 'penicillin' can either refer to several variants of penicillin available, or to the group of antibiotics derived from the penicillins.
The antibacterial effect of penicillin was discovered by Alexander Fleming in 1929. He noted that a fungal colony had grown as a contaminant on an agar plate streaked with the bacterium Staphylococcus aureus, and that the bacterial colonies around the fungus were transparent, because their cells were lysing. Fleming had devoted much of his career to finding methods for treating wound infections, and immediately recognised the importance of a fungal metabolite that might be used to control bacteria. The substance was named penicillin, because the fungal contaminant was identified as Penicillium notatum. Fleming found that it was effective against many Gram positive bacteria in laboratory conditions, and he even used locally applied, crude preparations of this substance, from culture filtrates, to control eye infections. However, he could not purify this compound because of its instability, and it was not until the period of the Second World War (1939-1945) that two other British scientists, Florey and Chain, working in the USA, managed to produce the antibiotic on an industrial scale for widespread use. All three scientists shared the Nobel Prize for this work, and rightly so - penicillin rapidly became the wonder drug which saved literally millions of lives. It is still a front line antibiotic, in common use for some bacterial infections although the development of penicillin-resistance in several pathogenic bacteria now limits its effectiveness.
During World War II, penicillin made a major difference in the number of deaths and amputations caused by infected wounds amongst Allied forces. Availability was severely limited, however, by the difficulty of manufacturing large quantities of penicillin and by the rapid renal clearance of the drug necessitating frequent dosing. Penicillins are actively secreted and about 80% of a penicillin dose is cleared within three to four hours of administration. During those times it became common procedure to collect the urine from patients being treated so that the penicillin could be isolated and reused.
This was not a satisfactory solution, however, so researchers looked for a way to slow penicillin secretion. They hoped to find a molecule that could compete with penicillin for the organic acid transporter responsible for secretion such that the transporter would preferentially secrete the competitive inhibitor. The uricosuric agent probenecid proved to be suitable. When probenecid and penicillin are concomitantly administered, probenecid competitively inhibits the secretion of penicillin, increasing its concentration and prolonging its activity. The advent of mass-production techniques and semi-synthetic penicillins solved supply issues, and this use of probenecid declined. Probenecid is still clinically useful, however, for certain infections requiring particularly high concentrations of penicillins.
The chemical structure of penicillin was determined by Dorothy Crowfoot Hodgkin in the early 1940s, enabling synthetic production. A team of Oxford research scientists led by Australian Howard Walter Florey and including Ernst Boris Chain and Norman Heatley discovered a method of mass producing the drug. Florey and Chain shared the 1945 Nobel prize in medicine with Fleming for this work. Penicillin has since become the most widely used antibiotic to date and is still used for many Gram-positive bacterial infections.
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About - The History of Penicillin
The search for antibiotics began in the late 1800s, with the growing acceptance of the germ theory of disease, a theory which linked bacteria and other microbes to the causation of a variety of ailments. As a result, scientists began to devote time to searching for drugs that would kill these disease-causing bacteria.
The Microbial World - Penicillin and other Antibiotics
The phenomenal success of penicillin led to the search for other antibiotic-producing microorganisms, especially from soil environments. One of the early successes (1943) was the discovery of streptomycin from a soil actinomycete, Streptomyces griseus. Actinomycetes are bacteria that produce branching filaments rather like fungal hyphae, but only about 1 micrometre diameter. They also produce large numbers of dry, powdery spores from their aerial hyphae.
Penicillin - The First Miracle Drug
An example of the importance of preserving the world's biodiversity occurred in 1996, in New York state. Students at Cornell University collected a fungus that finally made it possible to identify the two very different life stages of the mold that produces the drug cyclosporin. Cyclosporin prevents the rejection of transplanted organs. Without it, transplant operations would be impossible.